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Diet and carcinogenesis of gastric cancer

Article in Current Opinion in Gastroenterology · September 2022

DOI: 10.1097/MOG.0000000000000875

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REVIEW

CURRENT
OPINION Diet and carcinogenesis of gastric cancer
Gautam Maddineni a, Jesse J. Xie b,c, Bhaumik Brahmbhatt a
and Pritesh Mutha b,c

Purpose of review
Several recent studies have corroborated a strong association between diet and gastric cancer risk;
investigators have also identified dietary factors that protect against gastric cancer. This review summarizes
the literature on this topic and guides future research directions.
Recent findings
High-salt intake disrupts the gastric mucosal defense barrier, promoting Helicobacter pylori colonization
and penetration of other carcinogenic compounds. Processed foods, processed meats, red meat, alcohol,
foods with high dietary fat, and dietary cholesterol increase the risk of gastric carcinogenesis. On the other
hand, increased consumption of fruits, vegetables, whole grains, nuts, and a low-salt diet may offer a
protective effect.
Summary
Despite decreases in gastric cancer incidence because of increased identification and treatment of
H. pylori, gastric cancer remains one of the most common cancers worldwide with a high mortality rate.
This disturbing statistic highlights the importance of reducing and eliminating other risk factors for gastric
cancer. There is a strong body of evidence that alcohol, processed foods, high salt intake, high fat intake,
and foods with animal products (meats, eggs, and dairy) increase the risk of gastric cancer. A diet that is
high in whole grains, fruits, vegetables, nuts and is low in salt may reduce the risk of gastric cancer.
Keywords
carcinogenesis, diet, gastric adenocarcinoma, gastric cancer

INTRODUCTION predisposes to chronic inflammation, and impaired

Helicobacter pylori is the single most important risk
factor for the development of gastric adenocarci-
noma, accounting for 80–90% of distal adenocarci-
noma [1]. The prevention and treatment of H. pylori
has led to a significant decline in gastric cancer inci-
dence. Despite this steady decline, gastric cancer
remains the fifth leading cancer and the third leading
cause of cancer deaths worldwide [1]. These findings
highlight the importance of reducing and eliminat-
ing other risk factors for gastric cancer. Other gastric
cancer risk factors include tobacco, alcohol, obesity,
and diet. Diet is a significant but under-recognized
risk factor for gastric cancer. In this review, we sum-
marize recent publications on dietary gastric cancer
risk factors as well as dietary protective factors.
RISK FACTORS
Salt and Helicobacter pylori
High salt intake is associated with an increased
incidence of gastric cancer. A high salt intake is
proposed to break down the mucosal barrier, which
mucosal defense mechanisms that allow for
enhanced H. pylori colonization. Mucosal barrier
disruption can also potentiate the penetration of
known carcinogens such as N-methyl-N-nitro-nitro-
soguanidine [2]. Because many salted and preserved
foods also contain nitrite, the combination of salt
and nitrites act synergistically to promote gastric
carcinogenesis [3]. A recent meta-analysis that
included 26 prospective studies with almost five
million individuals reported an increased risk of
gastric cancer with both high and moderate salt
intake. High but not moderate pickled food intake
a
Division of Gastroenterology and Hepatology, Department of Internal
Medicine, Mayo Clinic, Jacksonville, Florida, bDivision of Gastroenter-
ology and Hepatology, Virginia Commonwealth University and cDivision
of Gastroenterology and Hepatology, McGuire VA Medical Center,
Richmond, Virginia, USA
Correspondence to Pritesh Mutha, MD, DipABLM, MPH, 11206 Tip-
perty trl, Richmond, TX 77407, USA. Tel: +1 908 821 7164;
e-mail: pritesh45@gmail.com
Curr Opin Gastroenterol 2022, 38:588–591
DOI:10.1097/MOG.0000000000000875

www.co-gastroenterology.com Volume 38  Number 6  November 2022

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Despite advances in H. pylori eradication, gastric
cancer remains one of the most common and lethal
cancers worldwide.
 Processed foods with preservatives such as nitrates and
salts, and animal food products such as dairy, eggs,
and meat increase the risk of gastric cancer.
 A diet rich in whole grains, fruits, vegetables, and nuts,
and low in salt may protect against gastric cancer.
was associated with increased gastric cancer risk.
Interestingly, salted fish intake was not associated
with increased gastric cancer risk. Seventeen of the
26 studies were from Asian countries, which does
limit the generalizability of the findings among
&
Western countries [4 ].
Nitrates, meat, and fish
Nitrates, which are subsequently converted to nitrites
in the digestive tract, are frequently used in the food
industry as a meat preservative. A diet high in nitrates
leads to the formation of carcinogenic N-nitroso
compounds (NOC) in the gastrointestinal tract. This
effect is enhanced in the presence of high heme iron
concentrations, as can occur with a diet high in red
meats and processed meats. The Iowa Women’s study
is a prospective study of 42 000 women followed via
food questionnaires since 1986. Consistent with pre-
vious reports, they recently reported an increased risk
of gastric cancer in adjusted models with high nitrite
intake from processed meats [hazard ratio 2.2, 95%
&
confidence interval (CI) 1.2–4.3] [5 ]. In a meta-anal-
ysis that included 232 studies with over 33 million
participants, red meat intake more than four times a
week increased the odds of developing gastric cancer,
although the results were not statistically significant
[odds ratio (OR) of 1.31, 95% CI 0.87–1.96) [6]. In the
same study, consumption of unsalted, uncured fish
did not appear to be protective or harmful with
regards to gastric cancer risk [6].
Alcohol
Laszkowska et al. recently published results from
over 470 000 individuals who participated in the
National Health and Nutrition Examination Survey
(NHANES) from 1999 to 2010. Heavy alcohol use
(defined as more than five drinks per day) was
associated with an increased risk of gastric cancer
(OR 3.13, 95% CI 1.15–8.64). There was no
increased risk of gastric cancer between a lifetime
0267-1379 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Diet and carcinogenesis of gastric cancer Maddineni et al.
alcohol intake of less than 12 alcoholic drinks versus
more than 12 drinks [7 ].
&
Dietary fats and cholesterol
Increased total dietary fat intake leads to oxidative
stress, which results in systemic inflammation that
could increase the risk of carcinogenesis. A meta-
analysis of 22 observational studies identified
increased gastric cancer risk with fat intake more
than 20 g/day [8]. Gastric cancer risk varied depend-
ing on the type of fat consumption: saturated fat
intake was associated with an increased risk of gastric
cancer [risk ratio (RR) 1.31, CI 1.09–1.58]. On the
other hand, polyunsaturated and vegetable fats
(found in foods such as tree nuts, olive oil, and fatty
&
fish) reduced gastric cancer risk [8,9 ]. There was no
association identified between the intake of mono-
unsaturated fat and animal fats and gastric cancer [8].
Dietary cholesterol might play a role in cancer
development via changes in lipid metabolism, which
are related to cellular inflammation [10]. An increase
in total cholesterol and low-density lipoprotein (LDL)
as well as a decrease in high-density lipoprotein (HDL)
could induce the production of inflammatory bio-
markers, such as interleukin-6 and tumor necrosis
factor-a [11]. Cholesterol is only found in animal
products – meat, fish, poultry, dairy, and eggs. There
is no cholesterol in plant-based foods, even in high-
fat plant foods such as avocados, nuts, and seeds. Yet
vegan diets high in saturated fats (such as coconut oil)
can predispose to high serum cholesterol levels
because the main fatty acid of coconut oil, lauric acid,
is a key substrate in apoliprotein-A1 and apoliprotein-
B synthesis, which in turn are crucial molecules in
the synthesis of LDL and HDL [12,13]. In a meta-
analysis of 14 case–control studies, high cholesterol
consumption was associated with a nonlinear dose–
response relationship with gastric cancer. Higher
intakes of dietary cholesterol were associated with
a 35% increased risk of gastric cancer (OR 1.35, CI
&
1.29–1.62) [14 ]. However, there were significant
inconsistencies between studies included in the
meta-analysis. Furthermore, after adjusting for
H. pylori, there was no association between dietary
&
cholesterol and gastric cancer [14 ].
PROTECTIVE FACTORS
Mediterranean diet
The Mediterranean diet consists heavily of vegeta-
bles, whole grains, legumes, fish, and olive oil,
which are high in polyunsaturated fat and low in
saturated fats and nitrites. A recent Spanish study
classified 459 participants into low, medium, and
www.co-gastroenterology.com 589
Stomach and duodenum
high adherence to the Mediterranean diet using five
different diet adherence indices. The study showed
significantly decreased gastric cancer risk, both car-
dia and noncardia subtypes, in those with the high-
&
est adherence [15 ].
Fruits and vegetables
Insufficient intake of total fruits and vegetables has
long been linked to increased gastric cancer risk. The
Stomach cancer Pooling (SToP) Project, a global
consortium focused on the epidemiological study
of gastric cancer, recently published data showing a
significantly reduced risk of gastric cancer in those
with the highest tertile consumption of fruits (0.76,
CI 0.64–0.90), vegetables (OR 0.68, CI 0.56–0.84),
and combined fruits and vegetables (OR 0.61, CI
&
0.49–0.75) versus those in the lowest tertile [16 ].
Whole grains
A systematic review by Gaesser noted that each
30 g/day intake of whole-grain is associated with a
7% reduction in overall cancer mortality risk, and
a 13–39% gastric cancer risk reduction when com-
paring highest versus lowest whole-grain consump-
&
tion groups [17 ].
Nuts
A recent meta-analysis of five studies that assessed
the association between tree nut intake and gastric
cancer found an inverse association between tree
nut consumption and total cancer risk (RR 0.88, CI
0.79–0.99), as well as gastric cancer risk (RR 0.83, CI
&
0.71–0.97) [9 ].
Nonalcoholic beverages
Studies assessing the impact of coffee on gastric
cancer have yielded mixed results. The heterogene-
ity of data, as well as confounders such as diet,
alcohol use, quantity of tobacco use, and types of
coffee consumed limit our understanding of the
relationship between coffee and gastric cancer. A
significant impact on gastric cancer risk was not
seen with black tea or green tea [6].
Supplements and micronutrients
In a recent study including 374 gastric cancer
patients and 754 control subjects, both higher total
dietary iron (OR 0.65, CI 0.45–0.94) and dietary
nonheme iron (OR 0.64, CI 0.44–0.92) were asso-
ciated with significantly lower gastric cancer risk
&
[18 ]. In a cohort of 51 895 subjects, a serum vitamin
590 www.co-gastroenterology.com
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
D level of more than 20 ng/ml was associated with a
lower risk of gastric cancer when compared with a
serum vitamin D level of less than 12 ng/ml (OR 0.57,
&
CI 0.23–1.00) [19 ]. Vitamin C and ascorbic acid have
been proposed to decrease the risk of gastric cancer.
High-dose oral ascorbic acid can act as a pro-oxidant
by reacting with heme iron in meats, leading to lipid
peroxidation and hydroxyl radical formation. But
when ascorbic acid is combined with polyphenols,
as found in fruits and vegetables, they act synergisti-
&&
cally to prevent lipid peroxidation [20 ]. Therefore,
intake of ascorbic acid from fruits and vegetables may
be preferable to synthetic ascorbic acid as it acts
collectively with carotenoids, polyphenols, flavo-
noids, and other phytochemicals. Though ascorbic
acid offers an attractive mechanism for gastric cancer
prevention, further research is needed to establish an
association and to assess whether dietary ascorbic
acid truly offers an advantage over ascorbic acid sup-
plementation.
Macronutrients
A recent case–control study identified a positive
association with gastric cancer among those in
the highest tertile intake of sucrose, protein, choles-
terol, and percentage calories from protein versus
those in the lowest tertile. They also found a neg-
ative association between gastric cancer and calories
obtained from carbohydrates [21 ].
&
CONCLUSION
Recent original studies and meta-analyses have clari-
fied the important role of diet and gastric cancer,
both in terms of risk factors and protective factors.
Current evidence supports reduced consumption of
salt, saturated fats, alcohol, red meat, processed and
cured meats to ameliorate gastric cancer risk. A diet
that is high in whole-grain, fruits, and vegetables
may protect against gastric cancer. Certain micro-
nutrients may play a role in reducing gastric cancer
risk. The Mediterranean diet is associated with
reduced gastric cancer risk. Whole food plant-based
diets (WFPBD) avoid processed foods (hence the
term ‘whole-foods’), meat, eggs, and dairy. Such
diets are typically low in salt, nitrites, and saturated
fat and rich in unsaturated fats, fruits, grains, and
vegetables and should, in theory, protect against
gastric cancer. However, studies are needed to clarify
such a protective effect with WFPBD. The interplay
between diet, the gut microbiome, and gastric can-
cer risk remains incompletely explored. Overall,
current studies of the gastric bacterial microbiome
do not provide convincing evidence to expand
the role of the gastric microbiome in cancer
Volume 38  Number 6  November 2022

pathogenesis beyond what is directly attributable to
the oncogenic potential of H. pylori and its role in
persistent acute-on-chronic inflammation [22].
The incidence rate of gastric cancer has
decreased dramatically over the last few decades,
in large measures because of the success in H. pylori
& indicators in a healthy family population: the STANISLAS cohort. Athero-
eradication [23 ]. However, gastric cancer remains a
major contributor to oncological deaths worldwide,
and modifiable risk factors remain underutilized.
Utilizing food as ‘preventive medicine’ carries a
significant untapped potential to further decrease
gastric cancer incidence and mortality.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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